Parkinson's disease (PD) is a neurodegenerative disorder affecting one million people in North America. There is no known cause for most cases of PD although environmental factors have been implicated in the majority of cases. We have preliminary evidence that parkinsonism is three to ten times more common in career welders than the general population. This application consists of a cohort study to test the hypothesis that the prevalence of parkinsonism is increased in a dose-dependent manner relative to non-exposed persons of similar age and gender. For our first specific aim we will perform a population based epidemiological study of the prevalence of parkinsonism in career welders and non-exposed referents. We will assemble a population based cohort of 875 workers and retirees (members of the International Brotherhood of Boilermakers) and 200 same-sex, nearest-age sibling referents with no prior welding history. Movement disorders specialists will perform all evaluations and ratings will be verified by a movement disorders specialist who will review a videotaped examination. Prevalence of parkinsonism will be compared between welders and the non-welder reference cohort. For the second specific aim of this study, an industrial hygienist will reconstruct subject welding exposure from a detailed exposure questionnaire in all exposed subjects. Subjects will be grouped into tertiles of exposure using a Job Exposure Matrix to determine if there is a dose-response relationship between welding exposure and parkinsonism. The research team represents a collaboration of movement disorders specialists, epidemiologists, industrial hygienists, and industry leaders. Demonstrating a definitive relationship between welding and parkinsonism will have substantial public health impact since the majority of these cases should be preventable through worksite modifications. The cohort assembled will provide unique opportunities for future research projects into gene-environment interactions and exposure related neuroimaging changes. [unreadable] [unreadable] [unreadable]